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Hall R, Patel K, Poullis A, Pollok R, Honap S. Separating Infectious Proctitis from Inflammatory Bowel Disease-A Common Clinical Conundrum. Microorganisms 2024; 12:2395. [PMID: 39770599 PMCID: PMC11678827 DOI: 10.3390/microorganisms12122395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 11/19/2024] [Accepted: 11/20/2024] [Indexed: 01/11/2025] Open
Abstract
Proctitis refers to inflammation in the rectum and may result in rectal bleeding, discharge, urgency, tenesmus, and lower abdominal pain. It is a common presentation, particularly in genitourinary medicine and gastroenterology, as the two most common causes are sexually transmitted infections and inflammatory bowel disease. The incidence of infective proctitis is rising, particularly amongst high-risk groups, including men who have sex with men, those with HIV seropositive status, and those participating in high-risk sexual behaviours. The most commonly isolated organisms are Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema palladium, herpes simplex virus, and Mycoplasma genitalium. Recently, proctitis was also identified as a common feature during the Mpox outbreak. Distinguishing infective proctitis from inflammatory bowel disease remains a significant clinical challenge as there is significant overlap in the clinical presentation and their endoscopic and histological features. This review compares and highlights the distinguishing hallmarks of both inflammatory and infective causes of proctitis. It provides a practical guide to describe the key features that clinicians should focus on in both clinical and key diagnostic investigations to avoid potential misdiagnosis.
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Affiliation(s)
- Richard Hall
- Department of Gastroenterology, St George’s University Hospital, London SW17 0QT, UK; (R.H.)
| | - Kamal Patel
- Department of Gastroenterology, St George’s University Hospital, London SW17 0QT, UK; (R.H.)
| | - Andrew Poullis
- Department of Gastroenterology, St George’s University Hospital, London SW17 0QT, UK; (R.H.)
| | - Richard Pollok
- Department of Gastroenterology, St George’s University Hospital, London SW17 0QT, UK; (R.H.)
- Institute of Infection and Immunity, St George’s University, London SW17 0RE, UK
| | - Sailish Honap
- Department of Gastroenterology, St George’s University Hospital, London SW17 0QT, UK; (R.H.)
- School of Immunology and Microbial Sciences, King’s College London, London SE1 9NH, UK
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Miyazawa A, Nambu R, Shimizu H, Kudo T, Nishizawa T, Kumagai H, Hagiwara SI, Kaji E, Mizuochi T, Kurasawa S, Kakuta F, Ishige T, Shimizu T, Iwama I, Arai K. Long-Term Course and Prognostic Factors in Pediatric Ulcerative Proctitis: A Multicenter Cohort Study. Inflamm Bowel Dis 2024:izae266. [PMID: 39561101 DOI: 10.1093/ibd/izae266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Indexed: 11/21/2024]
Abstract
BACKGROUND Although ulcerative proctitis (UP) in children is considered relatively mild, some patients have proximal disease extension and require immunosuppressive treatment. We investigated clinical characteristics and course of refractory UP in a multicenter pediatric cohort. METHODS Analyzing data obtained between 2013 and 2022 at 10 institutions specializing in pediatric inflammatory bowel disease, we elucidated natural history and factors predicting a need for immunosuppressive UP treatment. We compared patients given immunosuppressants and/or biologic agents (immunosuppressive treatment group) with those given 5-aminosalicylic acid (5-ASA) alone (5-ASA group). RESULTS Fifty-five patients were followed for 3.5 years. The median Pediatric Ulcerative Colitis Activity Index at diagnosis was 20. The commonest treatment, 5-ASA suppository monotherapy in 40% of patients, showed the worst compliance. Clinical remission was achieved at least once in 95% of all patients. Disease extension beyond the splenic flexure occurred in 51%. Immunosuppressive treatment was given to 37%; biologic agents were used for 18%. Rates of endoscopically demonstrated inflammation, including Ra/Rs at diagnosis and extension beyond the left-sided colon, were higher in the immunosuppressive treatment group (70% vs 38%, P < 0.05; 95% vs 27%, P < 0.0001). The log-rank test and multivariate Cox proportional hazards regression showed that time to first clinical remission exceeding 3 months predicted the need for biologics. CONCLUSION The typical initial treatment of pediatric UP was 5-ASA suppositories, despite poor compliance. Biologics or other immunosuppressive treatments were needed in 37% of patients. Close follow-up with adjustment of treatment should be considered in children with UP as its clinical course varies.
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Affiliation(s)
- Ayako Miyazawa
- Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, 1-2, Shintoshin, Chuo-ku, Saitama City, Saitama 330-8777, Japan
| | - Ryusuke Nambu
- Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, 1-2, Shintoshin, Chuo-ku, Saitama City, Saitama 330-8777, Japan
| | - Hirotaka Shimizu
- Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-City, Tokyo 157-8535, Japan
| | - Takahiro Kudo
- Department of Pediatrics, Juntendo University Faculty of Medicine, 3-1-3, Hongo, Bunkyo City, Tokyo 113-0033, Japan
| | - Takuya Nishizawa
- Department of Pediatrics, Gunma University Graduate School of Medicine, 3-39-15, Showamachi, Maebashi, Gunma 371-8511, Japan
| | - Hideki Kumagai
- Department of Pediatrics, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi 329-0431, Japan
| | - Shin-Ichiro Hagiwara
- Department of Gastroenterology, Nutrition and Endocrinology, Osaka Women's and Children's Hospital, 840, Murodocho, Izumi, Osaka 594-1101, Japan
| | - Emiri Kaji
- Department of Pediatrics, Osaka Medical and Pharmaceutical University, 2-7, Daigakumachi, Takatsuki, Osaka 569-0801, Japan
| | - Tatsuki Mizuochi
- Department of Pediatrics and Child Health, Kurume University School of Medicine, 67, Asahimachi, Kurume, Fukuoka 830-0011, Japan
| | - Shingo Kurasawa
- Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano 390-0802, Japan
| | - Fumihiko Kakuta
- Department of General Pediatrics and Gastroenterology, Miyagi Children's Hospital, 4-3-17, Ochiai, Aoba Ward, Sendai, Miyagi 989-3126, Japan
| | - Takashi Ishige
- Department of Pediatrics, Gunma University Graduate School of Medicine, 3-39-15, Showamachi, Maebashi, Gunma 371-8511, Japan
| | - Toshiaki Shimizu
- Department of Pediatrics, Juntendo University Faculty of Medicine, 3-1-3, Hongo, Bunkyo City, Tokyo 113-0033, Japan
| | - Itaru Iwama
- Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, 1-2, Shintoshin, Chuo-ku, Saitama City, Saitama 330-8777, Japan
| | - Katsuhiro Arai
- Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-City, Tokyo 157-8535, Japan
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Ye K, Jin Z, Chen Q, Cen L, Pan J, Zhou T, Jiang W, Liu Z, Luo L, Shen Z. Natural History and Longitudinal Outcomes of Patients with Mild-to-Moderate Ulcerative Proctitis or Ulcerative Proctosigmoiditis: A Single-Center, Retrospective Study. Dig Dis Sci 2024; 69:3701-3709. [PMID: 39215867 DOI: 10.1007/s10620-024-08615-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 08/21/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Ulcerative proctitis (UP) and ulcerative proctosigmoiditis (UPS) are special forms of ulcerative colitis. The disease burdens of UP and UPS are increasing. However, the natural history and prognosis of patients with mild-to-moderate UP or UPS have been poorly studied. AIMS The aim of this study is to evaluate the characteristics, short-term and long-term outcomes of patients with mild-to-moderate UP or UPS followed at a single center over a period of 3 years. METHODS A retrospective study of patients with UP and UPS followed at a single center from 2021 to 2023 was performed. After scanning for inclusion and exclusion criteria, patient demographics and clinical data were collected. Disease severity was accessed by Myao endoscopy scores and ulcerative colitis endoscopic index of severity. Endoscopic improvement was defined as decreased scores at the last follow-up. Disease extension was defined as endoscopic evidence of a greater extent of disease at the last follow-up. RESULTS A total of 414 patients were included for evaluation, of which 292 patients (70.53%) were at mild disease stage, and 122 patients (29.47%) had moderate diseases. At the last follow-up, 315 patients (76.09%) showed endoscopic improvement, and 247 patients (59.66%) showed endoscopic remission. An overall extension rate of 11.11% was observed at the last follow-up. Subgroup analysis revealed a better prognosis in younger patients. The disease extension rate was higher in moderate group and symptomatic patients. CONCLUSION Promising outcomes were observed in patients with mild-to-moderate ulcerative proctitis or ulcerative proctosigmoiditis. Disease severity and symptoms are correlated with the risk of extension.
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Affiliation(s)
- Kexin Ye
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China
| | - Zhenhe Jin
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China
| | - Qichen Chen
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China
| | - Li Cen
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China
| | - Jiaqi Pan
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China
| | - Tianyu Zhou
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China
| | - Wenxi Jiang
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China
| | - Zhaoxue Liu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China
| | - Linwen Luo
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China
| | - Zhe Shen
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, China.
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Ferreiro-Iglesias R, Porto Silva S, Marín S, Casanova MJ, Mañosa M, González-Muñoza C, de Francisco R, Caballol B, Arias L, Piqueras M, Zabana Y, Rivero M, Calvet X, Mesonero F, Varela Trastoy P, Busta Nistal R, Gómez Perosanz R, Vega P, Gonzalez-Vivo M, Iborra M, Bermejo F, Madero L, Rodríguez-Lago I, Rodríguez Gonzalez M, Vera I, Ponferrada Díaz Á, Vela M, Torrealba Medina L, Van Domselaar M, Gomollón F, Iglesias E, Gisbert JP, Calafat M, Giordano A, Pérez-Martínez I, Ricart E, Sicilia B, Mena R, Esteve M, Rivas C, Brunet-Mas E, Fernández C, de Jorge Turrión MÁ, Velayos Jiménez B, Quiñones Calvo M, Regueiro Expósito C, Márquez-Mosquera L, Nos P, Granja A, Gutiérrez A, Cabriada JL, Hervías Cruz D, Calvo M, Pérez Pérez J, Rodríguez Díaz Y, Busquets Casal D, Menacho M, Leal C, Lucendo AJ, Royo V, Olivares S, Álvarez Herrero B, Carrillo-Palau M, Gilabert Álvarez P, Manceñido Marcos N, Martínez-Pérez TDJ, Muñoz Villafranca MC, Almela P, Argüelles-Arias F, Legido J, Fuentes Coronel AM, Nieto L, Domènech E, Barreiro-de Acosta M. Need for therapeutic escalation in patients with refractory ulcerative proctitis: Results from the PROCU study of the ENEIDA registry. Aliment Pharmacol Ther 2024; 60:604-612. [PMID: 38943230 DOI: 10.1111/apt.18133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 02/12/2024] [Accepted: 06/08/2024] [Indexed: 07/01/2024]
Abstract
BACKGROUND Ulcerative proctitis (UP) can have a milder, less aggressive course than left-sided colitis or extensive colitis. Therefore, immunosuppressants tend to be used less in patients with this condition. Evidence, however, is scarce because these patients are excluded from randomised controlled clinical trials. Our aim was to describe the characteristics of patients with refractory UP and their disease-related complications, and to identify the need for immunosuppressive therapies. METHODS We identified patients with UP from the prospective ENEIDA registry sponsored by the GETECCU. We evaluated socio-demographic data and complications associated with immunosuppression. We defined immunosuppression as the use of immunomodulators, biologics and/or small molecules. We used logistic regression to identify factors associated with immunosuppressive therapy. RESULTS From a total of 34,716 patients with ulcerative colitis, we identified 6281 (18.1%) with UP; mean ± SD age 53 ± 15 years, average disease duration of 12 ± 9 years. Immunosuppression was prescribed in 11% of patients, 4.2% needed one biologic agent and 1% needed two; 2% of patients required hospitalisation, and 0.5% underwent panproctocolectomy or subtotal colectomy. We identified 0.2% colorectal tumours and 5% extracolonic tumours. Patients with polyarthritis (OR 3.56, 95% CI 1.86-6.69; p < 0.001) required immunosuppressants. CONCLUSIONS Among patients with refractory UP, 11% required immunosuppressant therapy, and 4.2% required at least one biologic agent.
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Affiliation(s)
- Rocío Ferreiro-Iglesias
- Fundación Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS), Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
| | - Sol Porto Silva
- Fundación Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS), Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
| | - Sandra Marín
- UCO, IMIBIC, Hospital Universitario Reina Sofía, Córdoba, Spain
| | - María José Casanova
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Madrid, Spain
| | - Míriam Mañosa
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
| | - Carlos González-Muñoza
- Hospital Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain
| | - Ruth de Francisco
- Hospital Universitario Central de Asturias, and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | - Berta Caballol
- CIBERehd. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain
| | - Lara Arias
- Hospital Universitario de Burgos, Burgos, Spain
| | | | - Yamile Zabana
- CIBERhed, Hospital Universitari Mutua Terrassa, Barcelona, Spain
- Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Montserrat Rivero
- Grupo de Investigación Clínica y Traslacional en Enfermedades Digestivas, Instituto de Investigación Valdecilla (IDIVAL), Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Xavier Calvet
- Universitat Autónoma de Barcelona, Barcelona, Spain
- CIBERehd, Institut d'Investigació i Innovació Parc Taulí, Departament de Medicina. Parc Taulí, Hospital Universitari, Sabadell, Spain
| | - Francisco Mesonero
- Universidad de Alcalá de Henares, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | | | | | | | - Pablo Vega
- Complexo Hospitalario Universitario de Ourense, Ourense, Spain
| | - Maria Gonzalez-Vivo
- IMIM Hospital del Mar Medical Research Institute, Hospital del Mar, Barcelona, Spain
| | - Marisa Iborra
- Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Fernando Bermejo
- Hospital Universitario de Fuenlabrada e Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain
| | - Lucía Madero
- CIBERehd. Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
| | - Iago Rodríguez-Lago
- Hospital Universitario de Galdakao, Biobizkaia Health Research Institute, Galdakao, Spain
| | | | - Isabel Vera
- Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
| | | | - Milagros Vela
- Hospital Nuestra señora de la Candelaria, Tenerife, Spain
| | | | | | - Fernando Gomollón
- CIBERehd. Hospital Clínico Universitario Lozano Blesa, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain
| | - Eva Iglesias
- UCO, IMIBIC, Hospital Universitario Reina Sofía, Córdoba, Spain
| | - Javier P Gisbert
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Madrid, Spain
| | - Margalida Calafat
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
| | - Antonio Giordano
- Hospital Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain
| | - Isabel Pérez-Martínez
- Hospital Universitario Central de Asturias, and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | - Elena Ricart
- CIBERehd. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain
| | | | - Raquel Mena
- Consorci Sanitari de Terrassa CST, Barcelona, Spain
| | - Maria Esteve
- CIBERhed, Hospital Universitari Mutua Terrassa, Barcelona, Spain
| | - Coral Rivas
- Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Eduard Brunet-Mas
- CIBERehd, Institut d'Investigació i Innovació Parc Taulí, Departament de Medicina. Parc Taulí, Hospital Universitari, Sabadell, Spain
| | - Cristina Fernández
- Universidad de Alcalá de Henares, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | | | | | | | | | | | - Pilar Nos
- Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - Alicia Granja
- Hospital Universitario de Fuenlabrada e Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain
| | - Ana Gutiérrez
- CIBERehd. Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
| | - José Luis Cabriada
- Hospital Universitario de Galdakao, Biobizkaia Health Research Institute, Galdakao, Spain
| | | | - Marta Calvo
- Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
| | | | | | | | | | - Carles Leal
- Universitat Central de Catalunya. Consorci Hospitalari de Vic. Universitat de Vic, Barcelona, Spain
| | - Alfredo J Lucendo
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Hospital General de Tomelloso, Ciudad Real, Spain
| | - Vanesa Royo
- Hospital Universitario Son Espases, Palma, Spain
| | | | | | | | | | | | | | | | - Pedro Almela
- Hospital General Universitario de Castellón, Castellón, Spain
| | | | | | | | - Laura Nieto
- Fundación Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS), Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
| | - Eugeni Domènech
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
- Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Manuel Barreiro-de Acosta
- Fundación Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS), Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
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Peyrin-Biroulet L, Dubinsky MC, Sands BE, Panés J, Schreiber S, Reinisch W, Feagan BG, Danese S, Yarur AJ, D’Haens GR, Goetsch M, Wosik K, Keating M, Lazin K, Wu J, Modesto I, McDonnell A, Bartolome L, Vermeire S. Efficacy and Safety of Etrasimod in Patients with Moderately to Severely Active Isolated Proctitis: Results From the Phase 3 ELEVATE UC Clinical Programme. J Crohns Colitis 2024; 18:1270-1282. [PMID: 38613425 PMCID: PMC11324338 DOI: 10.1093/ecco-jcc/jjae038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 02/08/2024] [Indexed: 04/15/2024]
Abstract
BACKGROUND AND AIMS Pivotal trials in ulcerative colitis have historically excluded patients with isolated proctitis. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis. This post hoc analysis assessed efficacy and safety of etrasimod 2 mg once daily in patients with isolated proctitis (centrally read) from the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials. METHODS Patients, including those with isolated proctitis (<10 cm rectal involvement) who met all other inclusion criteria in ELEVATE UC 52 and ELEVATE UC 12, were randomised 2:1 to receive etrasimod or placebo. Primary, secondary and other identified efficacy endpoints and safety were assessed. RESULTS We analysed data from 64 and 723 patients at Week 12 (both trials pooled), and 36 and 397 patients at Week 52 (ELEVATE UC 52 only) with isolated proctitis and more extensive colitis (≥10 cm rectal involvement), respectively. Patients with isolated proctitis receiving etrasimod demonstrated significant improvements versus placebo, including clinical remission rates at Weeks 12 (42.9% vs 13.6%) and 52 (44.4% vs 11.1%), endoscopic improvement (52.4% vs 22.7%) at Week 12 and bowel urgency numerical rating scale score at Week 12 (all p < 0.01). Generally similar trends were observed in patients with more extensive colitis. Safety was consistent across subgroups, with no new findings. CONCLUSIONS Etrasimod demonstrated significant improvements versus placebo in patients with isolated proctitis, and those with more extensive disease, in most efficacy endpoints at Week 12 and 52. Clinicaltrials.gov: NCT03945188; NCT03996369.
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Affiliation(s)
- Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- INSERM, NGERE, University of Lorraine, F-54000 Nancy, France
- INFINY Institute, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- Groupe Hospitalier privé Ambroise Paré - Hartmann, Paris IBD Center, 92200 Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC, Canada
| | - Marla C Dubinsky
- Susan and Leonard Feinstein IBD Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Bruce E Sands
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Julian Panés
- Formerly Department of Gastroenterology, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | - Stefan Schreiber
- Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel University, Kiel, Germany
| | - Walter Reinisch
- Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Brian G Feagan
- Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada
- Alimentiv Inc, London, ON, Canada
| | - Silvio Danese
- Division of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita Salute San Raffaele University, Milan, Italy
| | - Andres J Yarur
- Inflammatory Bowel Disease Center and Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Geert R D’Haens
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | | | | | | | | | | | | | | | | | - Séverine Vermeire
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
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6
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Gros B, Ross H, Nwabueze M, Constantine-Cooke N, Derikx LAAP, Lyons M, O’Hare C, Noble C, Arnott ID, Jones GR, Lees CW, Plevris N. Long-term outcomes and predictors of vedolizumab persistence in ulcerative colitis. Therap Adv Gastroenterol 2024; 17:17562848241258372. [PMID: 39086990 PMCID: PMC11289824 DOI: 10.1177/17562848241258372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 05/13/2024] [Indexed: 08/02/2024] Open
Abstract
Background Long-term vedolizumab (VDZ) outcomes in real-world cohorts have been largely limited to 1-year follow-up, with few bio-naïve patients or objective markers of inflammation assessed. Objectives We aimed to assess factors affecting VDZ persistence including clinical, biochemical and faecal biomarker remission at 1, 3 and 5 years. Design We performed a retrospective, observational, cohort study. Methods All adult inflammatory bowel disease (IBD) patients who had received VDZ induction for ulcerative colitis (UC)/IBD-unclassified (IBDU) were included. Baseline phenotype and follow-up data were collected via a review of electronic medical records. Results We included 290 patients [UC n = 271 (93.4%), IBDU n = 19 (6.6%)] with a median time on VDZ of 27.6 months (interquartile range: 14.4-43.2). At the end of follow-up, a total of 157/290 (54.1%) patients remained on VDZ. The median time to discontinuation was 14.1 months (7.0-23.3). Previous exposure to ⩾1 advanced therapy, steroid use at baseline and disease extension (E3 and E2 versus E1) were independent predictors for worse VDZ persistence. Clinical remission (partial Mayo < 2) was 75.7% (171/226), 72.4% (157/217) and 70.2% (127/181) at years 1, 3 and 5, respectively. Steroid use during maintenance VDZ therapy occurred in 31.7% (92/290), hospitalization in 15.5% (45/290) and surgery in 3.4% (10/291). The rate of serious adverse events was 1.2 per 100 patient-years of follow-up. Conclusion VDZ effectiveness appears enduring with favourable long-term safety profile. VDZ persistence was influenced by previous exposure to biologics/small molecules, disease distribution and steroid use at baseline in our study.
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Affiliation(s)
- Beatriz Gros
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
- Department of Gastroenterology; Liver and Digestive Diseases Networking Biomedical Research Centre (CIBEREHD), Madrid, Spain and Hepatology, Reina Sofía University Hospital, Córdoba, Spain
| | - Hannah Ross
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
| | - Maureen Nwabueze
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
| | - Nathan Constantine-Cooke
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK
- Centre for Genomics and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK
| | - Lauranne A. A. P. Derikx
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Mathew Lyons
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
| | - Claire O’Hare
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
- Edinburgh Pharmacy Unit, Western General Hospital, Edinburgh, UK
| | - Colin Noble
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
| | - Ian D. Arnott
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
| | - Gareth-Rhys Jones
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
- Centre for Inflammation Research, The Queen’s Medical Research Institute, University of Edinburgh, Scotland, UK
| | - Charlie W. Lees
- Edinburgh IBD Unit, Western General Hospital, NHS Lothian, Crewe Road, Edinburgh EH4 2XU, UK
- Centre for Genomics and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK
| | - Nikolas Plevris
- Edinburgh IBD Unit, Western General Hospital, Edinburgh, Scotland, UK
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De Deo D, Dal Buono A, Gabbiadini R, Spaggiari P, Busacca A, Masoni B, Ferretti S, Bezzio C, Armuzzi A. Management of proctitis in ulcerative colitis and the place of biological therapies. Expert Opin Biol Ther 2024; 24:443-453. [PMID: 38874980 DOI: 10.1080/14712598.2024.2369189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Accepted: 06/13/2024] [Indexed: 06/15/2024]
Abstract
INTRODUCTION Approximately 20-30% of the patients with ulcerative colitis (UC) may present with isolated proctitis. Ulcerative proctitis (UP) is a challenging condition to manage due to its significant burden in terms of disabling symptoms. AREAS COVERED PubMed was searched up to March 2024 to identify relevant studies on UP. A comprehensive summary and critical appraisal of the available data on UP are provided, highlighting emerging treatments and areas for future research. EXPERT OPINION Patients with UP are often undertreated, and the disease burden is often underestimated in clinical practice. Treat-to-target management algorithms can be applied to UP, aiming for clinical remission in the short term, and endoscopic remission and maintenance of remission in the long term. During their disease, approximately one-third of UP patients require advanced therapies. Escalation to biologic therapy is required for refractory or steroid dependent UP. For optimal patient care and management of UP, it is necessary to include these patients in future randomized clinical trials.
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Affiliation(s)
- Diletta De Deo
- IBD Center, Humanitas Research Hospital - IRCCS, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Arianna Dal Buono
- IBD Center, Humanitas Research Hospital - IRCCS, Rozzano, Milan, Italy
| | | | - Paola Spaggiari
- Department of Pathology, Humanitas Research Hospital, Rozzano Milan, Italy
| | - Anita Busacca
- IBD Center, Humanitas Research Hospital - IRCCS, Rozzano, Milan, Italy
| | - Benedetta Masoni
- IBD Center, Humanitas Research Hospital - IRCCS, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Silvia Ferretti
- IBD Center, Humanitas Research Hospital - IRCCS, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Cristina Bezzio
- IBD Center, Humanitas Research Hospital - IRCCS, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Alessandro Armuzzi
- IBD Center, Humanitas Research Hospital - IRCCS, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
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8
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Singh A, Mahajan R, Midha V, Kaur K, Singh D, Kaur R, Garg S, Arora K, Bansal N, Sood A. Effectiveness of Tofacitinib in Ulcerative Proctitis Compared to Left Sided Colitis and Pancolitis. Dig Dis Sci 2024; 69:1389-1402. [PMID: 38358458 DOI: 10.1007/s10620-024-08276-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 01/03/2024] [Indexed: 02/16/2024]
Abstract
BACKGROUND Ulcerative proctitis (UP), though associated with high symptom burden and poor quality of life, is excluded from most of the randomized controlled trials in UC, including the OCTAVE trials. We aimed to analyse the effectiveness of tofacitinib in UP, and compare it to that in left sided colitis (LSC) and pancolitis (PC). METHODS This was a prospective cohort study. Patients with either steroid-dependent or refractory ulcerative colitis, who received tofacitinib, were divided into three groups based on the disease extent [UP, LSC and PC]. The primary outcome was comparison of proportion of patients in clinical remission in the three groups, at weeks 8, 16 and 48. Safety outcomes were reported using incidence rate per patient year of exposure. RESULTS Clinical remission was achieved in 47%(15/32), 24%(23/94), and 43%(23/54) of patients at week 8, 56%(18/32), 37%(35/94), and 56%(30/54) of patients at week 16, and 59%(19/32), 38%(36/94), and 24%(13/54) of patients at week 48 in groups UP, LSC and PC, respectively. Corticosteroid-free clinical remission rates were significantly higher in patients in groups UP at week 48. Five (15%) patients with UP were primary non-responders to tofacitinib at week 16, while three (9%) patients had secondary loss of response at week 48. The probability of sustained clinical response was highest in patients with UP. Patients with UP had the lowest incidence of adverse effects. CONCLUSION The effectiveness of tofacitinib in inducing and maintaining clinical remission is greater in patients with UP compared to LSC and PC.
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Affiliation(s)
- Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, 141001, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, 141001, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Kirandeep Kaur
- Department of Pharmacology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Dharmatma Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, 141001, India
| | - Ramandeep Kaur
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, 141001, India
| | - Shreya Garg
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Kirti Arora
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Namita Bansal
- Research and Development Centre, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, 141001, India.
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Uzzan M, Nachury M, Nuzzo A, Amiot A, Caron B, Benezech A, Buisson A, Bouguen G, Le Berre C, Reenaers C, Le Cosquer G, Savoye G, Charkaoui M, Vidon M, Guillo L, Fumery M, Peyrin-Biroulet L, Kirchgesner J, Bouhnik Y. Tofacitinib for Patients with Anti-TNF Refractory Ulcerative Proctitis: A Multicentre Cohort Study from the GETAID. J Crohns Colitis 2024; 18:424-430. [PMID: 37796025 DOI: 10.1093/ecco-jcc/jjad169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 09/10/2023] [Accepted: 10/04/2023] [Indexed: 10/06/2023]
Abstract
BACKGROUND Although ulcerative proctitis [UP] can dramatically impair quality of life, treatment efficacy has been poorly investigated in UP as it was historically excluded from phase 2/3 randomised controlled trials in ulcerative colitis. Our aim was to assess the effectiveness and safety of tofacitinib for the treatment of UP. METHODS We conducted a retrospective, multicentre study in 17 GETAID centres, including consecutive patients with UP treated with tofacitinib. The primary endpoint was steroid-free remission between Week 8 and Week 14, defined as a partial Mayo score of 2 [and no individual subscore above 1]. Secondary outcomes included clinical response and steroid-free remission after induction and at 1 year. RESULTS All the 35 enrolled patients previously received anti-tumour necrosis factor [TNF] therapy and 88.6% were exposed to at least two lines of biologics. At baseline, the median partial Mayo score was 7 (intequartile range [IQR] [5.5-7]). After induction [W8-W14], 42.9% and 60.0% of patients achieved steroid-free remission and clinical response, respectively. At 1 year, the steroid-free clinical remission and clinical response rates were 39.4% and 45.5%, respectively, and 51.2% [17/33] were still receiving tofacitinib treatment. Survival without tofacitinib withdrawal was estimated at 50.4% (95% confidence interval [CI] [35.5-71.6]) at 1 year. Only a lower partial Mayo at baseline was independently associated with remission at induction (0dds ratio [OR] = 0.56 for an increase of 1, (95% CI [0.33-0.95], p = 0.03). Five [14.3%] adverse events were reported, with one leading to treatment withdrawal [septic shock secondary to cholecystitis]. CONCLUSION Tofacitinib may offer a therapeutic option for patients with refractory UP.
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Affiliation(s)
- Mathieu Uzzan
- University of Lille, CHU Lille, Institute for Translational Research in Inflammation, Lille, France
| | - Maria Nachury
- University of Lille, CHU Lille, Institute for Translational Research in Inflammation, Lille, France
| | - Alexandre Nuzzo
- Department of Gastroenterology, Hopital Beaujon, Universite de Paris, France
| | - Aurélien Amiot
- Department of Gastroenterology, Hopitaux Universitaires Bicêtre, Universite Paris Est Creteil and Universite Paris Saclay, Centre for Research in Epidemiology and Population Health, Le Kremlin Bicêtre, France
| | - Bénédicte Caron
- Department of Gastroenterology, Nancy University Hospital, and INSERM, NGERE, University of Lorraine, Nancy, France
| | - Alban Benezech
- Department of Gastroenterology, Centre Hospitalier Avignon, Avignon, France
| | - Anthony Buisson
- Université Clermont Auvergne, Service d'Hépato-Gastroentérologie, Clermont-Ferrand, France
| | | | - Catherine Le Berre
- Institut des Maladies de l'Appareil Digestif, Hépato-Gastro-Entérologie et Assistance Nutritionnelle,Nantes Université, Nantes, France
| | - Catherine Reenaers
- Department of Gastroenterology and Hepatology, CHU Liège, University of Liège, Liège, Belgium
| | - Guillaume Le Cosquer
- Department of Gastroenterology and Pancreatology, Hôpital Rangueil, Université Toulouse Paul Sabatier, Toulouse, France
| | - Guillaume Savoye
- Department of Gastroenterology Rouen University Hospital, UMR 1073 University of Rouen Normandy, Rouen, France
| | - Maeva Charkaoui
- Department of Hepatogastroenterology, Dijon University Hospital, Dijon, France
| | - Mathias Vidon
- Department of Gastroenterology. Hopital Intercommunal de Créteil, Créteil, France
| | - Lucas Guillo
- Department of Gastroenterology, University Hospital of Marseille Nord, University of Aix-Marseille, Marseille, France
| | - Mathurin Fumery
- Department of Gastroenterology, Amiens University Hospital, and UMR I01, PERITOX, Jules Verne University of Picardy, Amiens, France
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, and INSERM, NGERE, University of Lorraine, Nancy, France
| | - Julien Kirchgesner
- Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Université, Department of Gastroenterology, Hôpital Saint-Antoine, Paris, France
| | - Yoram Bouhnik
- Paris IBD Center, Groupe Hospitalier Privé Ambroise Paré - Hartmann, Neuilly sur Seine, France
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Lemmens P, Louis E, Van Moerkercke W, Pouillon L, Somers M, Peeters H, Vanden Branden S, Busschaert J, Baert F, Cremer A, Potvin P, Dewit S, Colard A, Swinnen J, Lambrecht G, Claessens C, Willandt B, Dewint P, Van Dyck E, Sabino J, Vermeire S, Ferrante M. Outcome of Biological Therapies and Small Molecules in Ulcerative Proctitis: A Belgian Multicenter Cohort Study. Clin Gastroenterol Hepatol 2024; 22:154-163.e3. [PMID: 37442318 DOI: 10.1016/j.cgh.2023.06.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 06/17/2023] [Accepted: 06/25/2023] [Indexed: 07/15/2023]
Abstract
BACKGROUND & AIMS Several advanced therapies (biologic therapies and small molecules) have been approved for the treatment of moderate-to-severe ulcerative colitis. The registration trials for these agents typically excluded patients with isolated proctitis, leaving an evidence gap. We evaluated efficacy and safety of advanced therapies in patients with ulcerative proctitis (UP). METHODS This multicenter retrospective cohort study included consecutive patients with active UP (Mayo endoscopy subscore of ≥2, rectal inflammation up to 15 cm) initiating advanced therapy, after failing conventional therapy. The primary end point was short-term steroid-free clinical remission (total Mayo score ≤2 with no individual subscore >1). In addition, drug persistence and relapse-free and colectomy-free survival were assessed. Both binary logistic and Cox regression analyses were performed. RESULTS In total, 167 consecutive patients (52.0% female; median age 41.0 years; 82.0% bionaive) underwent 223 courses of therapy for UP (38 adalimumab, 14 golimumab, 54 infliximab, 9 ustekinumab, 99 vedolizumab, 9 tofacitinib). The primary end point was achieved with 36.3% of the treatment courses, and based on multivariate analysis, more commonly attained in bionaive patients (P = .001), patients treated with vedolizumab (P = .001), patients with moderate endoscopic disease activity (P = .002), and a body mass index <25 kg/m2 (P = .018). Drug persistence was significantly higher in patients treated with vedolizumab (P < .001) and patients with a shorter disease duration (P = .006). No new safety signals were observed. CONCLUSIONS Advanced therapies are also efficacious and safe in patients with ulcerative colitis limited to the rectum. Therefore, the inclusion of patients with UP in future randomized-controlled trials should be considered.
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Affiliation(s)
- Pauline Lemmens
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Edouard Louis
- Department of Gastroenterology, CHU Liege and Liege University, Liege, Belgium
| | | | - Lieven Pouillon
- Department of Gastroenterology, Imelda Hospital, Bonheiden, Belgium
| | - Michael Somers
- Department of Gastroenterology, University Hospital Antwerp, Antwerp, Belgium
| | - Harald Peeters
- Department of Gastroenterology, University Hospital Gent, Gent, Belgium
| | | | | | - Filip Baert
- Department of Gastroenterology, AZ Delta, Roeselare, Belgium
| | - Anneline Cremer
- Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium
| | - Philippe Potvin
- Department of Gastroenterology, AZ Rivierenland, Bornem, Belgium
| | - Sophie Dewit
- Department of Gastroenterology, Noorderhart Maria Hospital, Pelt, Belgium
| | - Arnaud Colard
- Department of Gastroenterology, Centre Hospitalier Chrétien - Clinique St Joseph, Liege, Belgium
| | - Jo Swinnen
- Department of Gastroenterology, Sint Franciscus Hospital, Heusden-Zolder, Belgium
| | - Guy Lambrecht
- Department of Gastroenterology, AZ Damiaan, Oostende, Belgium
| | | | | | - Pieter Dewint
- Department of Gastroenterology, University Hospital Antwerp, Antwerp, Belgium; Department of Gastroenterology, AZ Maria Middelares, Gent, Belgium
| | - Evi Van Dyck
- Department of Gastroenterology, AZ Klina, Brasschaat, Belgium
| | - Joao Sabino
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium; Department of Chronic Diseases and Metabolism (CHROMETA), Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - Séverine Vermeire
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium; Department of Chronic Diseases and Metabolism (CHROMETA), Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
| | - Marc Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium; Department of Chronic Diseases and Metabolism (CHROMETA), Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
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11
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Tal N, Tzivinikos C, Gasparetto M, Serban DE, Zifman E, Hojsak I, Ledder O, Yerushalmy Feler A, Rolandsdotter H, Aloi M, Bramuzzo M, Buderus S, Lionetti P, Norsa L, Norden C, Urlep D, Romano C, Shaoul R, Martinez-Vinson C, Karoliny A, De Greef E, Kang B, VIčková E, Alvisi P, Kori M, Tavares M, Weiss B, Hussey S, Qamhawi ME, Palomino Pérez LM, Henderson P, Parmar R, Miele E, Rinawi F, Lozano-Ruf A, Zamvar V, Kolho KL, Shouval DS. Clinical Features and Natural History of Paediatric Patients with Ulcerative Proctitis: A Multicentre Study from the Paediatric IBD Porto Group of ESPGHAN. J Crohns Colitis 2023; 17:1939-1948. [PMID: 37392064 DOI: 10.1093/ecco-jcc/jjad111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Indexed: 07/02/2023]
Abstract
BACKGROUND AND AIMS Ulcerative proctitis [UP] is an uncommon presentation in paediatric patients with ulcerative colitis. We aimed to characterize the clinical features and natural history of UP in children, and to identify predictors of poor outcomes. METHODS This was a retrospective study involving 37 sites affiliated with the IBD Porto Group of ESPGHAN. Data were collected from patients aged <18 years diagnosed with UP between January 1, 2016 and December 31, 2020. RESULTS We identified 196 patients with UP (median age at diagnosis 14.6 years [interquartile range, IQR 12.5-16.0]), with a median follow-up of 2.7 years [IQR 1.7-3.8]. The most common presenting symptoms were bloody stools [95%], abdominal pain [61%] and diarrhoea [47%]. At diagnosis, the median paediatric ulcerative colitis activity index [PUCAI] score was 25 [IQR 20-35], but most patients exhibited moderate-severe endoscopic inflammation. By the end of induction, 5-aminosalicylic acid administration orally, topically or both resulted in clinical remission rates of 48%, 48%, and 73%, respectively. The rates of treatment escalation to biologics at 1, 3, and 5 years were 10%, 22%, and 43%, respectively. In multivariate analysis, the PUCAI score at diagnosis was significantly associated with initiation of systemic steroids, or biologics, and subsequent acute severe colitis events and inflammatory bowel disease-associated admission, with a score ≥35 providing an increased risk for poor outcomes. By the end of follow-up, 3.1% of patients underwent colectomy. Patients with UP that experienced proximal disease progression during follow-up [48%] had significantly higher rates of a caecal patch at diagnosis and higher PUCAI score by the end of induction, compared to those without progression. CONCLUSION Paediatric patients with UP exhibit high rates of treatment escalation and proximal disease extension.
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Affiliation(s)
- Noa Tal
- Institute of Gastroenterology, Nutrition and Liver Disease, Schneider Children's Medical Center, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Christos Tzivinikos
- Paediatric Gastroenterology Department, Al Jalila Children's Specialty Hospital, Mohammed Bin Rashid University, Dubai, United Arab Emirates
| | - Marco Gasparetto
- Barts Health NHS Trust, The Royal London Children's Hospital, Department of Paediatric Gastroenterology, Queen Mary University of London, Centre for Immunobiology, Blizard Institute, London, UK
| | - Daniela E Serban
- 2nd Clinic of Pediatrics, 'Iuliu Hatieganu' University of Medicine and Pharmacy, Emergency Clinical Hospital for Children, Cluj-Napoca, Romania
| | - Eyal Zifman
- Pediatric Gastroenterology Unit, Meir Medical Center, Kfar-Saba, Israel
| | - Iva Hojsak
- Referral Center for Pediatric Gastroenterology and Nutrition, Children's Hospital Zagreb, Zagreb, Croatia
| | - Oren Ledder
- The Juliet Keidan Institute of Pediatric Gastroenterology & Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Anat Yerushalmy Feler
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Pediatric Gastroenterology Institute, 'Dana-Dwek' Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Helena Rolandsdotter
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
- Sachs' Children and Youth Hospital, Department of Gastroenterology, Södersjukhuset, Stockholm, Sweden
| | - Marina Aloi
- Pediatric Gastroenterology, Hepatology and Nutrition Institute, Sapienza University of Rome, Rome, Italy
| | - Matteo Bramuzzo
- Institute for Maternal and Child Health, IRCCS 'Burlo Garofolo', Trieste, Italy
| | | | - Paolo Lionetti
- Department NEUROFARBA, University of Florence, Meyer Children's Hospital, Florence, Italy
| | - Lorenzo Norsa
- Pediatric Hepatology, Gastroenterology and Transplantation Unit, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Christoph Norden
- Department of Pediatrics, Hvidovre University Hospital, Copenhagen, Hvidovre, Denmark
| | - Darja Urlep
- Pediatric Gastroenterology and Liver Unit, University Children's Hospital of the University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Claudio Romano
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood 'G. Barresi', University of Messina, Messina, Italy
| | - Ron Shaoul
- Pediatric Gastroenterology and Nutrition Institute, Ruth Children's Hospital of Haifa, Rambam Medical Center, Faculty of Medicine, Technion, Haifa, Israel
| | - Christine Martinez-Vinson
- Service de Gastroentérologie et Nutrition Pédiatriques, Hôpital Universitaire Robert-Debré, Paris, France
| | - Anna Karoliny
- Heim Pál National Pediatric Institute, Budapest, Hungary
| | - Elisabeth De Greef
- Department of Paediatric Gastroenterology and Nutrition, Kidz Health Castle UZ Brussels, Free University Brussels, Brussels, Belgium
| | - Ben Kang
- Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Eva VIčková
- Department of Pediatrics, 2nd Medical Faculty, Charles University and University Hospital Motol, Prague, Czech Republic
| | - Patrizia Alvisi
- Pediatric Gastroenterology Unit, Maggiore Hospital, Bologna, Italy
| | - Michal Kori
- Pdiatric Gastroenterology, Kaplan Medical Centre, Rehovot and the Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Marta Tavares
- Department of Pediatric Gastroenterology, Centro Materno Infantil do Norte, Centro Hospitalar e Universitário de Porto, Porto, Portugal
| | - Batia Weiss
- Division of Pediatric Gastroenterology and Nutrition, Edmond and Lily Safra Children's Hospital, Ramat Gan, Israel
| | - Seamus Hussey
- Children's Health Ireland, UCD and RCSI, Dublin, Ireland
| | - Maria E Qamhawi
- Department of Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children's Hospital, Karolinska University Hospital, StockholmSweden
| | - Laura M Palomino Pérez
- Gastroenterology and Nutrition Department, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
| | - Paul Henderson
- Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Children and Young People, Edinburgh, UK
| | - Raj Parmar
- Department of Pediatric Gastroenterology, Great North Children's Hospital, Newcastle, UK
| | - Erasmo Miele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples 'Federico II', Naples, Italy
| | - Firas Rinawi
- Pediatric Gastroenterology Unit, Emek Medical Center, Afula, Israel
- The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
| | - Ana Lozano-Ruf
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain
| | - Veena Zamvar
- Department of Paediatric Gastroenterology, Leeds Children's Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Kaija-Leena Kolho
- Children's Hospital, University of Helsinki, Helsinki, Finland
- Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland
| | - Dror S Shouval
- Institute of Gastroenterology, Nutrition and Liver Disease, Schneider Children's Medical Center, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Aruljothy A, Singh S, Narula N, Moran GW, Vuyyuru SK, Hogan M, Zayadi A, MacDonald JK, Caron B, Danese S, Biroulet LP, Ma C, Jairath V. Systematic review with meta-analysis: Medical therapies for treatment of ulcerative proctitis. Aliment Pharmacol Ther 2023; 58:740-762. [PMID: 37589498 PMCID: PMC11162959 DOI: 10.1111/apt.17666] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 05/27/2023] [Accepted: 07/28/2023] [Indexed: 08/18/2023]
Abstract
BACKGROUND Ulcerative proctitis (UP) is a common highly symptomatic form of ulcerative colitis that can be difficult to treat. AIM To assess the efficacy of medical treatments for UP. METHODS We searched MEDLINE, EMBASE, and CENTRAL on 23 November 2022 for randomised controlled trials (RCTs) of medical therapy for adults with UP. Primary outcomes included induction and maintenance of clinical remission. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for each outcome. RESULTS We included 53 RCTs (n = 4096) including 46 induction studies (n = 3731) and seven maintenance studies (n = 365). First-line therapies included topical 5-aminosalicylic acid (5-ASA), conventional corticosteroids, budesonide, and oral 5-ASA. Therapy for refractory UP included topical tacrolimus and small molecules. Topical 5-ASA was superior to placebo for induction (RR 2.72, 95% CI 1.94-3.82) and maintenance of remission (RR 2.09, 95% CI 1.26-3.46). Topical corticosteroids were superior to placebo for induction of remission (RR 2.83, 95% CI 1.62-4.92). Topical budesonide was superior to placebo for induction of remission (RR 2.34, 95% CI 1.44-3.81). Combination therapy with topical 5-ASA and topical corticosteroids was superior to topical monotherapy with either agent. Topical tacrolimus was superior to placebo. Etrasimod was superior to placebo for induction (RR 4.71, 95% CI 1.2-18.49) and maintenance of remission (RR 2.08, 95% CI 1.31-3.32). CONCLUSIONS Topical 5-ASA and corticosteroids are effective for active UP. Topical 5-ASA may be effective for maintenance of remission. Tacrolimus may be effective for induction of remission. Etrasimod may be effective for induction and for maintenance of remission. Trials should include UP to expand the evidence base for this under-represented population.
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Affiliation(s)
- Achuthan Aruljothy
- Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada
| | - Siddharth Singh
- Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California, USA
| | - Neeraj Narula
- Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
| | - Gordon W. Moran
- National Institute of Health Research Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals, Nottingham, UK
| | - Sudheer K. Vuyyuru
- Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada
- Alimentiv, Inc., London, Ontario, Canada
| | | | | | | | - Benedicte Caron
- Department of Gastroenterology, University of Lorraine, CHRU-Nancy, Nancy, France
- University of Lorraine, Inserm, NGERE, Nancy, France
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Laurent Peyrin Biroulet
- Department of Gastroenterology, University of Lorraine, CHRU-Nancy, Nancy, France
- University of Lorraine, Inserm, NGERE, Nancy, France
| | - Christopher Ma
- Alimentiv, Inc., London, Ontario, Canada
- Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Vipul Jairath
- Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada
- Alimentiv, Inc., London, Ontario, Canada
- Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
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13
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Kyriacou M, Radford S, Moran GW. Delphi consensus survey: the opinions of patients living with refractory ulcerative proctitis and the health care professionals who care for them. BMJ Open Gastroenterol 2023; 10:bmjgast-2023-001139. [PMID: 37225263 DOI: 10.1136/bmjgast-2023-001139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Accepted: 04/24/2023] [Indexed: 05/26/2023] Open
Abstract
BACKGROUND Refractory ulcerative proctitis presents a huge clinical challenge not only for the patients living with this chronic, progressive condition but also for the professionals who care for them. Currently, there is limited research and evidence-based guidance, resulting in many patients living with the symptomatic burden of disease and reduced quality of life. The aim of this study was to establish a consensus on the thoughts and opinions related to refractory proctitis disease burden and best practice for management. METHODS A three-round Delphi consensus survey was conducted among patients living with refractory proctitis and the healthcare experts with knowledge on this disease from the UK. A brainstorming stage involving a focus group where the participants came up with an initial list of statements was completed. Following this, there were three rounds of Delphi surveys in which the participants were asked to rank the importance of the statements and provide any additional comments or clarifications. Calculation of mean scores, analysis of comments and revisions were performed to produce a final list of statements. RESULTS In total, 14 statements were suggested by the focus group at the initial brainstorming stage. Following completion of three Delphi survey rounds, all 14 statements reached consensus following appropriate revision. CONCLUSIONS We established consensus on the thoughts and opinions related to refractory proctitis from both the experts who manage this disease and the patients living with it. This represents the first step towards developing clinical research data and ultimately the evidence needed for best practice management guidance of this condition.
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Affiliation(s)
- Maro Kyriacou
- Gastroenterology, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Shellie Radford
- Nottingham Digestive Diseases Centre, Translational Medical Sciences, University of Nottingham University Park Campus, Nottingham, UK
| | - Gordon W Moran
- Nottingham Digestive Diseases Centre, Translational Medical Sciences, University of Nottingham University Park Campus, Nottingham, UK
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14
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Wang CR, Tsai HW. Seronegative spondyloarthropathy-associated inflammatory bowel disease. World J Gastroenterol 2023; 29:450-468. [PMID: 36688014 PMCID: PMC9850936 DOI: 10.3748/wjg.v29.i3.450] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 11/18/2022] [Accepted: 12/21/2022] [Indexed: 01/12/2023] Open
Abstract
Seronegative spondyloarthropathy (SpA) usually starts in the third decade of life with negative rheumatoid factor, human leukocyte antigen-B27 genetic marker and clinical features of spinal and peripheral arthritis, dactylitis, enthesitis and extra-articular manifestations (EAMs). Cases can be classified as ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis, or juvenile-onset spondyloarthritis. Joint and gut inflammation is intricately linked in SpA and inflammatory bowel disease (IBD), with shared genetic and immunopathogenic mechanisms. IBD is a common EAM in SpA patients, while extraintestinal manifestations in IBD patients mostly affect the joints. Although individual protocols are available for the management of each disease, the standard therapeutic guidelines of SpA-associated IBD patients remain to be established. Nonsteroidal anti-inflammatory drugs are recommended as initial therapy of peripheral and axial SpA, whereas their use is controversial in IBD due to associated disease flares. Conventional disease-modifying anti-rheumatic drugs are beneficial for peripheral arthritis but ineffective for axial SpA or IBD therapy. Anti-tumor necrosis factor monoclonal antibodies are effective medications with indicated use in SpA and IBD, and a drug of choice for treating SpA-associated IBD. Janus kinase inhibitors, approved for treating SpA and ulcerative colitis, are promising therapeutics in SpA coexistent with ulcerative colitis. A tight collaboration between gastroenterologists and rheumatologists with mutual referral from early accurate diagnosis to appropriately prompt therapy is required in this complex clinical scenario.
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Affiliation(s)
- Chrong-Reen Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan
| | - Hung-Wen Tsai
- Department of Pathology, National Cheng Kung University Hospital, Tainan 70403, Taiwan
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Gaweł K, Dąbkowski K, Zawada I, Starzyńska T. Progression risk factors of ulcerative proctitis. Scand J Gastroenterol 2022; 57:1406-1411. [PMID: 35793351 DOI: 10.1080/00365521.2022.2094726] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. It is characterized by a chronic course with periods of aggravations and remissions. Among patients, 25-55% present with ulcerative proctitis (UP) at the time of diagnosis. UP is well-treated disease associated with a good prognosis. UP is characterized by a less aggressive course than the left-sided form of UC and pancolitis, with a good response to topical treatment. Moreover, UP is associated with a lower risk of severe aggravations and systemic and local complications and lower need for colectomy, hospitalization and glucocorticosteroids and immunosuppressive drugs, in comparison with more extensive forms of the disease. Thus, the key issue is to prognose the natural course of the disease in order to identify high-risk patients and apply biological or immunosuppressive treatment early to prevent the development of complications. In this review, we summarize the current knowledge about the natural course of UP and discuss risks and protective factors related to disease progression and current treatment concepts.
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Affiliation(s)
- Katarzyna Gaweł
- Department of Gastroenterology, Pomeranian Medical University, Szczecin, Poland
| | - Krzysztof Dąbkowski
- Department of Gastroenterology, Pomeranian Medical University, Szczecin, Poland
| | - Iwona Zawada
- Department of Gastroenterology, Pomeranian Medical University, Szczecin, Poland
| | - Teresa Starzyńska
- Department of Gastroenterology, Pomeranian Medical University, Szczecin, Poland
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16
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Caron B, Abreu MT, Siegel CA, Panaccione R, Sands BE, Dignass A, Turner D, Dotan I, Hart AL, Ahuja V, Allez M, Ananthakrishnan AN, Ghosh S, Griffiths AM, Halfvarson J, Kaser A, Kotze PG, Koutroubakis IE, Lakatos PL, Levine A, Lewis JD, Magro F, Mantzaris GJ, O'Morain C, Ran Z, Reinisch W, Rogler G, Sachar DB, Siegmund B, Silverberg MS, Sood A, Spinelli A, Steinwurz F, Tysk C, Yamamoto-Furusho JK, Schreiber S, Rubin DT, Sandborn WJ, Danese S, Peyrin-Biroulet L. IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis: The PROCTRIAL Consensus. Clin Gastroenterol Hepatol 2022; 20:2619-2627.e1. [PMID: 35189386 DOI: 10.1016/j.cgh.2022.02.032] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 02/07/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the Definition and endpoints for ulcerative PROCtitis in clinical TRIALs initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults. METHODS Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters. RESULTS The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity was proposed. Secondary endpoints that should be evaluated include endoscopic remission, histologic remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life. CONCLUSIONS In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the Definition and end points for ulcerative PROCtitis in clinical TRIALs consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials.
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Affiliation(s)
- Bénédicte Caron
- Nancy University Hospital, Department of Gastroenterology and University of Lorraine, Inserm, Nutrition-Génétique et Exposition aux Risques Environnementaux, F-54000 Nancy, France
| | - Maria T Abreu
- Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida
| | - Corey A Siegel
- Inflammatory Bowel Disease Center, Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
| | - Remo Panaccione
- Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
| | | | - Axel Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Goethe-University, Frankfurt am Main, Germany
| | - Dan Turner
- Juliet Keidan Institute of Pediatric Gastroenterology Hepatology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Iris Dotan
- Division of Gastroenterology, Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ailsa L Hart
- Inflammatory Bowel Disease Unit, St. Mark's Hospital, Harrow, United Kingdom
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Matthieu Allez
- Department of Gastroenterology, Hôpital Saint-Louis, Assistance Publique - Hôpitaux de Paris, INSERM U1160, Université de Paris, Paris, Île-de-France, France
| | - Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Subrata Ghosh
- College of Medicine and Health, University College Cork, Cork, Ireland
| | - Anne M Griffiths
- SickKids Inflammatory Bowel Disease Center, Division of Gastroenterology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
| | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Arthur Kaser
- University of Cambridge, Cambridge University Hospitals-Addenbrooke's Hospital, Cambridge, United Kingdom
| | - Paulo G Kotze
- Inflammatory Bowel Disease Outpatient Clinics, Colorectal Surgery Unit, Catholic University of Paraná, Curitiba, Brazil
| | - Ioannis E Koutroubakis
- Department of Gastroenterology, University Hospital of Heraklion, Medical School, University of Crete, Crete, Greece
| | - Peter L Lakatos
- Department of Medicine and Oncology, Semmelweis University, McGill University Health Center, Montreal General Hospital, Montreal, Canada
| | - Arie Levine
- Pediatric Gastroenterology Unit, Paediatric Inflammatory Bowel Diseases Research Center, Wolfson Medical Center, Holon, Israel
| | - James D Lewis
- Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Fernando Magro
- Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal; Department of Clinical Pharmacology, São João University Hospital Center (CHUSJ), Porto, Portugal; Faculty of Medicine, University of Porto, Portugal. Center for Health Technology and Services Research (CINTESIS), Porto, Portugal; Center for Health Technology and Services Research (CINTESIS), Porto, Portugal
| | - Gerassimos J Mantzaris
- Department of Gastroenterology, Evangelismos-Polykliniki General Hospital, Athens, Greece
| | - Colm O'Morain
- Faculty of Health Sciences, University of Dublin, Trinity College, Dublin, Ireland
| | - Zhihua Ran
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China
| | - Walter Reinisch
- Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Gerhard Rogler
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - David B Sachar
- Chief Emeritus of Gastroenterology and Professor of Medicine, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Britta Siegmund
- Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Department of Gastroenterology, Rheumatology and Infectious Disease, Campus Benjamin Franklin, Berlin, Germany
| | - Mark S Silverberg
- Mount Sinai Hospital Inflammatory Bowel Disease Centre, Toronto, Ontario, Canada
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiāna, Punjab, India
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Division of Colon and Rectal Surgery, Scientific Institute for Research, Hospitalization and Healthcare Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Flavio Steinwurz
- Department of Gastroenterology, Albert Einstein Israelite Hospital, São Paulo, Brazil
| | - Curt Tysk
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Jesus K Yamamoto-Furusho
- Inflammatory Bowel Disease Clinic, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpa, Mexico
| | - Stefan Schreiber
- Department of Internal Medicine, University Hospital Schleswig-Holstein, Kiel, Germany
| | - David T Rubin
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, Illinois
| | - William J Sandborn
- Division of Gastroenterology, University of California San Diego, La Jolla, California
| | - Silvio Danese
- Humanitas Research Hospital, University Vita-Salute San Raffaele, Milano, Italy
| | - Laurent Peyrin-Biroulet
- Nancy University Hospital, Department of Gastroenterology and University of Lorraine, Inserm, Nutrition-Génétique et Exposition aux Risques Environnementaux, F-54000 Nancy, France.
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Efficacy of the Panax Notoginseng Ejiao Suppository in the Treatment of Patients with Ulcerative Proctitis and Its Effect on Inflammatory Response and Immune Function. DISEASE MARKERS 2022; 2022:1479964. [PMID: 36188425 PMCID: PMC9519316 DOI: 10.1155/2022/1479964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 08/29/2022] [Accepted: 08/30/2022] [Indexed: 11/17/2022]
Abstract
Objective. To investigate the efficacy of the Panax notoginseng Ejiao suppository in patients with ulcerative proctitis and its effect on inflammatory response and immune function. Methods. This study recruited 100 patients with ulcerative proctitis who were hospitalized to our hospital’s anorectal outpatient department between May 2015 and October 2020. They were randomly separated into either a control or a study group, with 50 cases in each. The control group received the mesalazine suppository, whereas the study group received the Panax notoginseng Ejiao suppository. Outcome measures included clinical effectiveness, inflammatory response, and immunological state of patients. Results. The total efficiency in the study group was significantly higher than that in the control group (
). The Mayo score and Baron endoscopic score between the two groups were significantly decreased after treatment, with lower results in the study group (
). The inflammatory variables were dramatically reduced following therapy, with the study group doing worse. Following treatment, the number of Th 17 cells declined dramatically in both groups, while the proportion of Treg cells increased significantly, with greater alterations of Th17 cells and Treg cells observed in the study group than those in the control group (
). The Panax notoginseng Ejiao suppository resulted in significantly shorter time lapses before symptom alleviation and a lower incidence of recurrence at 6 months after treatment versus mesalazine suppository (
). Conclusion. In patients with ulcerative proctitis, the Panax notoginseng Ejiao suppository significantly improves clinical efficacy, reduces the incidence of recurrence, mitigates inflammatory response, and improves immune function.
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18
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Caron B, Sandborn WJ, Panaccione R, Schreiber S, Hart A, Solitano V, Danese S, Peyrin-Biroulet L. Efficacy of Pharmacological Agents for Ulcerative Proctitis: A Systematic Literature Review. J Crohns Colitis 2022; 16:922-930. [PMID: 34850857 DOI: 10.1093/ecco-jcc/jjab218] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 11/04/2021] [Accepted: 11/29/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Ulcerative proctitis is a common and often highly symptomatic form of inflammatory bowel disease. We performed a systematic review to assess the efficacy of different therapies in the management of patients with ulcerative proctitis. METHODS We identified randomized controlled trials in adults with ulcerative proctitis treated with oral or topical therapies for induction of response or remission, or prevention of relapse. RESULTS A total of 32 randomized controlled trials were included [27 induction/2839 participants, five maintenance/334 participants]. Follow-up varied from 3 to 8 weeks for induction, and from 6 to 24 months for maintenance of remission. 5-Aminosalicylic acid [5-ASA] suppository was the most frequently evaluated treatment [14/32, 43.7%], followed by steroid enema [7/32, 21.9%]. Topical 5-ASA demonstrated effectiveness for induction of clinical response or remission and prevention of relapse in several studies. Combined topical steroids and 5-ASA was more effective than topical 5-ASA or topical steroids alone to induce response [100% of patients for combination vs 70% for beclomethasone alone and 76% for 5-ASA alone]. One observational study suggested azathioprine may be effective in patients with ulcerative proctitis. Only two cohort studies evaluated the efficacy of tumour necrosis factor inhibitors in ulcerative proctitis. Small molecules, anti-integrins and anti-interleukin therapies have not been evaluated in isolated ulcerative proctitis. CONCLUSION The role of topical 5-ASA as a treatment for ulcerative proctitis has been confirmed in this systematic literature review, for induction and maintenance of remission. Future trials are needed to investigate the efficacy of more recent and upcoming drug classes in patients with ulcerative proctitis.
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Affiliation(s)
- Bénédicte Caron
- Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - William J Sandborn
- Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA
| | - Remo Panaccione
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Stefan Schreiber
- Department of Internal Medicine, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Ailsa Hart
- Inflammatory Bowel Diseases Unit, St Mark's Hospital, Harrow, UK
| | - Virginia Solitano
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milano, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France
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Juillerat P, Grueber MM, Ruetsch R, Santi G, Vuillèmoz M, Michetti P. Positioning biologics in the treatment of IBD: A practical guide - Which mechanism of action for whom?. CURRENT RESEARCH IN PHARMACOLOGY AND DRUG DISCOVERY 2022; 3:100104. [PMID: 35570855 PMCID: PMC9092374 DOI: 10.1016/j.crphar.2022.100104] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 04/04/2022] [Accepted: 04/24/2022] [Indexed: 12/30/2022] Open
Abstract
The number of available biological therapies have doubled over the last 10 years and the arrival of novel molecules (interleukin 23p19 inhibitors) is ongoing alongside the development of small molecules. As a result of this vast landscape of treatment, positioning advanced therapies (according to clinical situation, efficacy and safety) is of paramount importance to providing personalized, appropriate IBD treatment. In this publication the recent available literature is summarized for practical integration into clinical practice including comparative efficacy data, patient and disease demographics. We refer to recent publications and expert opinion in order to facilitate the decision making process of positioning biologicals IBD treatment.
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Affiliation(s)
- Pascal Juillerat
- Gastroenterology, Clinic for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Crohn and Colitis Center, Gastro-entérologie Beaulieu SA, Lausanne, Switzerland
| | - Maude Martinho Grueber
- Gastroenterology, Clinic for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Crohn and Colitis Center, Gastro-entérologie Beaulieu SA, Lausanne, Switzerland
| | - Roseline Ruetsch
- Crohn and Colitis Center, Gastro-entérologie Beaulieu SA, Lausanne, Switzerland
| | - Giulia Santi
- Gastroenterology, Clinic for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Marianne Vuillèmoz
- Crohn and Colitis Center, Gastro-entérologie Beaulieu SA, Lausanne, Switzerland
| | - Pierre Michetti
- Crohn and Colitis Center, Gastro-entérologie Beaulieu SA, Lausanne, Switzerland
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
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Verstockt B, Bressler B, Martinez-Lozano H, McGovern D, Silverberg MS. Time to Revisit Disease Classification in Inflammatory Bowel Disease: Is the Current Classification of Inflammatory Bowel Disease Good Enough for Optimal Clinical Management? Gastroenterology 2022; 162:1370-1382. [PMID: 34995534 DOI: 10.1053/j.gastro.2021.12.246] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Revised: 12/08/2021] [Accepted: 12/09/2021] [Indexed: 12/12/2022]
Abstract
Inflammatory bowel disease (IBD), historically subdivided into Crohn's disease and ulcerative colitis, is a very heterogeneous condition. While the tendency in medicine is to try to reduce complexity, IBD is a disease that cannot justify a one-size-fits-all principle. Our current clinical classification tools are suboptimal and need further refinement to capture, at least in part, the variety of phenotypes encountered in daily clinical practice. Although these revised classification tools alone will not be sufficient and should be complemented by more detailed molecular subclassifications, optimized clinical phenotypes can contribute to improved trial designs, future translational research approaches, and better treatment outcomes. In the current review, we discuss key clinical features important in IBD disease heterogeneity, tackle limitations of the current classification systems, propose some potential improvements, and raise priorities for future research in this domain.
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Affiliation(s)
- Bram Verstockt
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium; Department of Chronic Diseases and Metabolism, Katholieke Universiteit Leuven, Leuven, Belgium
| | - Brian Bressler
- Division of Gastroenterology, Department of Medicine, St. Paul's Hopsital, University of British Columbia, Vancouver, British Columbia, Canada
| | - Helena Martinez-Lozano
- Division of Gastroenterology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Dermot McGovern
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Mark S Silverberg
- Division of Gastroenterology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
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Michalopoulos G, Karmiris K. When disease extent is not always a key parameter: Management of refractory ulcerative proctitis. CURRENT RESEARCH IN PHARMACOLOGY AND DRUG DISCOVERY 2022; 3:100071. [PMID: 34988432 PMCID: PMC8695253 DOI: 10.1016/j.crphar.2021.100071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 11/29/2021] [Accepted: 12/02/2021] [Indexed: 10/27/2022] Open
Abstract
Background Patients with ulcerative proctitis represent a sub-group of ulcerative colitis patients with specific characteristics. Disease-related symptoms, endoscopic findings and patient's personality perspectives create a difficult-to-assess condition in certain cases. Objectives To summarize available evidence on the management of refractory ulcerative proctitis and provide insights in treatment options. Results /Conclusion: Topical therapy plays a central role due to the location of the disease. However, well-established treatment options may become exhausted in a considerable proportion of ulcerative proctitis patients, indicating the need to advance to more potent therapies in order to induce and maintain clinical response and remission in these refractory cases. Systemic corticosteroids, thiopurines, calcineurin inhibitors, biologic agents and small molecules have all been tested with variable success rates. Investigational interventions as well as surgical procedures are kept as the ultimate resort in multi-treatment resistant cases. Identifying early prognostic factors that herald a disabling disease progression will help in optimizing treatment and avoiding surgery.
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Affiliation(s)
- Georgios Michalopoulos
- Departments of Gastroenterology, Tzaneion General Hospital, Leoforos Afentouli, 18536, Piraeus, Greece
| | - Konstantinos Karmiris
- Departments of Gastroenterology, Venizeleio General Hospital, Knosos Avenue, P.O.Box 44, 71409, Heraklion, Crete, Greece
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Privitera G, Pugliese D, Lopetuso LR, Scaldaferri F, Papa A, Rapaccini GL, Gasbarrini A, Armuzzi A. Orphan patients with inflammatory bowel disease - when we treat beyond evidence. World J Gastroenterol 2021; 27:8047-8057. [PMID: 35068853 PMCID: PMC8704270 DOI: 10.3748/wjg.v27.i47.8047] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 07/12/2021] [Accepted: 12/08/2021] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic condition that requires continuous medical treatment. To date, the medical management of patients with moderately-to-severely active IBD who develop dependence or resistance to corticosteroids is based on immunomodulator drugs. Such therapies are licenced after passing through three phases of randomized controlled trials (RCTs), and are subsequently adopted in clinical practice. However, the real-life population of IBD patients who require these therapies can significantly differ from those included in RCTs. As a matter of fact, there is a number of exclusion criteria – nearly ubiquitous in all RCTs – that prevent the enrolment of specific patients: Chronic refractory pouchitis or isolated proctitis in ulcerative colitis, short-bowel syndrome and stomas in Crohn’s disease, ileorectal anastomosis in both ulcerative colitis and Crohn’s disease, and elderly age are some representative examples. In this frontier article, we aim to give an overview of current literature on this topic, in order to address the main knowledge gaps that need to be filled in the upcoming years.
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Affiliation(s)
- Giuseppe Privitera
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Daniela Pugliese
- CEMAD – IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome 00168, Italy
| | - Loris Riccardo Lopetuso
- CEMAD – IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche , Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome 00168, Italy
- Department of Medicine and Ageing Sciences, “G. d’Annunzio” University of Chieti-Pescara, Chieti 66100, Italy
- Center for Advanced Studies and Technology (CAST), “G.d’Annunzio” University of Chieti-Pescara, Chieti 66100, Italy
| | - Franco Scaldaferri
- CEMAD – IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome 00168, Italy
| | - Alfredo Papa
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome 00168, Italy
- CEMAD – IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome 00168, Italy
| | - Gian Lodovico Rapaccini
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome 00168, Italy
- CEMAD – IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome 00168, Italy
| | - Antonio Gasbarrini
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome 00168, Italy
- CEMAD – IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome 00168, Italy
| | - Alessandro Armuzzi
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome 00168, Italy
- CEMAD – IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome 00168, Italy
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Affiliation(s)
- Bella Ungar
- Department of Gastroenterology, Sheba Medical Center, Ramat Gan and Sackler Medical School, Tel Aviv Israel
| | - Uri Kopylov
- Department of Gastroenterology, Sheba Medical Center, Ramat Gan and Sackler Medical School, Tel Aviv Israel
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